Correlation between binding and dynamics at SH2 domain interfaces.
Protein recognition is a key determinant in regulating biological processes. Structures of complexes of interacting proteins provide significant insights into the mechanism of specific recognition. However, studies performed by modifying residues within a protein interface demonstrate that binding is not fully explained by these static pictures. Thus, structural data alone was not predictive of affinities in binding studies of phospholipase Cgamma1 and Syp phosphatase SH2 domains with phosphopeptides. NMR relaxation experiments probing dynamics of methyl groups of these complexes indicate a correlation between binding energy and restriction of motion at the interfacial region responsible for specific binding.
Kay
L E
LE
Protein Engineering Network Centres of Excellence and Department of Medical Genetics, University of Toronto, Ontario, Canada.
Muhandiram
D R
DR
Wolf
G
G
Shoelson
S E
SE
Forman-Kay
J D
JD
D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000737:chemistry*; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D051966:Phospholipase C gamma; D010748:Phosphopeptides / Q000737:chemistry*; D010750:Phosphoproteins / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*; D017479:Receptors, Platelet-Derived Growth Factor / Q000737:chemistry; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D013816:Thermodynamics; D010738:Type C Phospholipases / Q000737:chemistry*; D018909:src Homology Domains
D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D010748:Phosphopeptides; D010750:Phosphoproteins; D017479:Receptors, Platelet-Derived Growth Factor; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D054593:SH2 Domain-Containing Protein Tyrosine Phosphatases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma